Myocardial adrenergic and cholinergic receptor function in hypoxia: correlation with O₂ transport in exercise

Abstract

The time course of changes in rat myocardial alpha(1)- and beta-adrenoceptors and of muscarinic cholinergic (M-Ach) receptor characteristics was studied parallel with the changes in exercise systemic O(2) transport during a 21-day period of hypoxia (barometric pressure 380 Torr) to assess the effects of receptor modification during acclimatization on maximal exercise capacity. Hypoxia resulted in polycythemia, pulmonary hypertension, right ventricular hypertrophy, and transient left ventricular weight loss. Maximal O(2) consumption at 30 min of hypoxia was reduced to 60% of the normoxic value and remained unchanged. This was partly due to a gradual decrease in maximal cardiac output and heart rate (HR(max)), which offset the increase in blood O(2) content. HR(max) correlated positively (r = 0.994) with beta-adrenoceptor density and negatively (r = -0.964) with M-Ach-receptor density, suggesting that HR(max) reduction results from intrinsic changes in myocardial receptor characteristics leading to reduced responses to adrenergic stimulation and elevated responses to cholinergic stimulation. alpha-Adrenoceptor density in both ventricles increased initially to eventually fall below normoxic values. The dissociation between the different patterns of right and left ventricular weight and the similar pattern of alpha-adrenoceptor change in both ventricles do not support a role for these receptors on right ventricular myocardial hypertrophy.

Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics

“…As water consumption usually decreases at the beginning of hypoxic exposure, acetazolamide treatment started 2 days before hypoxia in the preventive group to obtain an adequate dose of acetazolamide. In curative-treated rats, the treatment began after 10 days of hypoxic exposure, as it has been previously reported that pulmonary hypertension as well as Hb concentration remain unchanged from day 10 to day 21 [1,8]. After the first day of acetazolamide treatment, we observed an important increase in water consumption in rats, demonstrating that acetazolamide was also taken well in curative treatment.…”

“…Both preventive groups received acetazolamide 2 days before entering the hypobaric chamber, while curative groups received acetazolamide after 10 days of hypoxic exposure, which has previously been shown to significantly increase pulmonary arterial pressure (PAP) [1]. Rats undergoing chronic hypoxic exposure were housed for 21 days in a hypoxic chamber connected to a gas pump where air was circulated at a pressure of 380 mmHg (5,500 m altitude above sea level).…”

“…[1,31]. A part of this increase is attributed to a higher Hct in acclimatised rats [31], but other factors are thought to be involved, such as an increase in adrenergic-mediated vasoconstrictor tone and/or vascular remodelling in the systemic circulation [31].…”

“…C hronic exposure to hypoxia induces polycythaemia and pulmonary hypertension in both humans and rats [1][2][3][4]. An excessive erythrocytosis (haemoglobin (Hb) concentration .21 g?dL -1 or haematocrit (Hct) concentration .63%) characterises Monge's disease or chronic mountain sickness [5].…”

Autonomic Nervous System

“…Favret et al [ 79 ], however, showed that the density of rat right ventricular β -adrenoceptors was signifi cantly elevated after just 30 min of hypoxia, but it subsequently declined to values below those found in normoxia.…”